Dimethylformamide → HCID 73427144, compound

HRID 1507551Notes

Reaction equation

HRID 1507551 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.O=S(Cl)Cl.CN(C=O)C.[NH2:20][C:21]1[CH:29]=[C:28]2[C:24]([C:25]([CH3:32])([CH3:31])[C:26](=[O:30])[NH:27]2)=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.ClCCl.O.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:31][C:25]1([CH3:32])[C:24]2[C:28](=[CH:29][C:21]([NH:20][C:5](=[O:7])[C:4]3[CH:8]=[CH:9][N:10]=[C:2]([CH3:1])[CH:3]=3)=[CH:22][CH:23]=2)[NH:27][C:26]1=[O:30]

Participants

10

Reactant 5

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 27628212-Methylpyridine-4-carboxylic acidHCID 135892296-Amino-3,3-dimethyl-1,3-dihydro-2H-indol-2-one

Product 1

HCID 73427144HCID 73427144, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 10340Sodium CarbonateSolvent

Procedure

To a suspension of 2-methylisonicotinic acid (175 mg, 1.28 mmol) in dry toluene (12.8 ml) was added SOCl2 (167 mg, 103 μl, 1.4 mmol) and dry DMF (9.33 mg, 9.89 μl, 128 μmol) under an argon atmosphere. The mixture was heated under reflux for 2 hours and the solvent was evaporated under reduced pressure. The residue was suspended in dry dichloromethane (3.51 ml) and a suspension of 6-amino-3,3-dimethylindolin-2-one (0.15 g, 851 μmol) and DIPEA (330 mg, 446 μl, 2.55 mmol) in dry dichloromethane (5 ml) was added portionwise. The suspension was stirred under an argon atmosphere at room temperature for 16 hours, then diluted with dichloromethane, water and 1 M aqueous sodium carbonate solution. The aqueous phase was extracted with dichloromethane. The combined organic layers were washed with 1 M aqueous sodium carbonate solution, dried over sodium sulfate, the solvent was evaporated and the residue purified by silica gel chromatography using dichloromethane/methanol as eluent. The title compound was obtained as brown solid (99 mg).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 2 hours
  3. customthe solvent was evaporated under reduced pressure
  4. additionwas added portionwise
  5. extractionThe aqueous phase was extracted with dichloromethane
  6. washThe combined organic layers were washed with 1 M aqueous sodium carbonate solution
  7. dry with materialdried over sodium sulfate
  8. customthe solvent was evaporated
  9. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-eb7734ccf06c42739902d770623a5306
Source dataset
uspto-grants-2015_12
Patent number
US09221816B2

Reaction notes

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